The long-term objective of this research is to provide insights into the phenomenon of malignant transformation of human epithelial cells. The approach which will be taken will be to establish an in vitro culture system of human epidermal cells which will proliferate and undergo terminal differentiation and to use this system to analyze the processes of human papilloma virus (HPV) infection and/or cellular transformation. In this way, it will be possible to determine how the state of differentiation can regulate viral gene expression and how viral transformation can affect the program of cellular differentiation. In general, the experimental procedures will evaluate the consequence of the interaction between HPV and cultures of human epidermal cells. Several different epidermal cell systems will be established, including normal, SV40 WT- and tsA-transformed, and papilloma tissue-derived. These cell systems will be characterized and then monitored for the ability to interact with and support the complete or partial expression of the HPV Genome. The transforming function(s) of HPV will also be evaluated in these culture systems. The effect of viral transformation on epidermal cell growth and terminal differentiation will be established by defining the spectrum of phenotypic properties which are expressed in the transformants. This system should provide an excellent in vitro model for evaluating the role of papilloma viruses in the induction of human malignancies.